2026-06-10T20:46:40Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/118212026-06-09T06:24:29Zcom_10259_6168com_10259_5086com_10259_2604col_10259_6169
High Expression of PAPP‐A Predicts Poor Outcomes in Oestrogen Receptor‐Positive Breast Cancer Patients
Mabruk, Zeanap
Bullock, Esme
Xiao, Xue
Guo, Jingjing
Zhu, Xuan
Gómez Cuadrado, Laura
Oxvig, Claus
Mallon, Elizabeth
Ammar, Aula
Malty, Amna
Pennel, Kathryn
Edwards, Joanne
Brunton, Valerie G.
Breast cancer
IGF-1 signalling
Invasive lobular carcinoma
Pregnancy-associated plasma protein-A
Introduction: Insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1R) signalling is activated in breast cancer and asso-ciated with disease progression. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that can cleave IGFbinding proteins leading to the release of bioactive IGF-1 and the subsequent activation of IGF-1 signalling. Here, we aimed toassess the prognostic significance of PAPP-A in breast cancer.Methods: Breast cancer tissue microarrays were stained for PAPP-A and expression correlated with survival and other clinicalfeatures. Analysis of publicly available data sets was carried out to determine associations between PAPPA and gene sets associ-ated with IGF-1/IGF-1R pathway activation.Results: PAPP-A was expressed in both the tumour and stromal compartments in breast cancer specimens and was higher inoestrogen receptor (ER)-negative (ER-) than ER-positive (ER+) cases. There was a significant association between high PAPP-Aexpression and reduced cancer-specific survival (CSS) in ER+ (HR 1.389, 95% CI 1.051–1.836, p = 0.021) but not ER- patients (HR1.040, 95% CI 0.712–1.598, p = 0.838). In a second cohort of ER+ invasive lobular carcinoma (ILC) PAPP-A expression was alsoassociated with reduced CSS (HR 1.765, 95% CI 1.098–2.836, p = 0.019). PAPPA correlated with REACTOME PI3K-AKT andIGF1R signalling gene sets in ER+ breast cancers.Conclusion: High expression of PAPP-A is associated with poor prognosis in ER+ breast cancer and correlates with IGF-1/IGF-1R pathway activation
2026-06-08
2026-06-08
2026-04
info:eu-repo/semantics/article
2045-7634
https://hdl.handle.net/10259/11821
10.1002/cam4.71815
2045-7634
eng
Cancer Medicine. V. 15, n. 4, art. e71815
https://doi.org/10.1002/cam4.71815
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Atribución 4.0 Internacional
Wiley